Tumor metastásico en tejido blando a nivel del sacro secundario a carcinoma de células claras de riñón. Reporte de caso / Metastatic tumor in soft tissue at the level of the sacrum secondary toclear cell carcinoma of the kidney. A case report

Introducción. El cáncer de riñón es la undécima neoplasia maligna más común en los Estados Unidos Mexicanos. El carcinoma de células claras de riñón (CCR) es considerado la estirpe más frecuente y representa el 2-3 % de todos los cánceres a nivel mundial. En el contexto de la enfermedad metastásica, por lo general se identifica un tumor renal primario y las metástasis se localizan en pulmón, hueso, hígado, cerebro y, raramente, en tejidos blandos. Los pacientes con metástasis a tejidos blandos no tienen síntomas en las etapas iniciales y generalmente se identifican sólo cuando las lesiones aumentan de tamaño o durante el estudio de la pieza de resección quirúrgica. Caso clínico. Se presenta el caso de una paciente en la séptima década de la vida, con una metástasis en tejidos blandos de la región sacra, de 10 años de evolución posterior a una nefrectomía secundario a CCR. Resultados. Hallazgos clínicos e imagenológicos de un tumor bien delimitado. Se realizó resección quirúrgica de la lesión, bajo anestesia regional, con extirpación completa. Conclusión. Se recomienda que los pacientes con un sitio metastásico resecable y solitario sean llevados a resección quirúrgica con márgenes libres, como fue el caso de nuestra paciente, por su fácil acceso y ser una lesión única. En el CCR, además de su tratamiento quirúrgico inicial, es indispensable una estrecha vigilancia con examen físico e imágenes transversales, para detectar la presencia de metástasis y con ello evitar tratamientos tardíos.

Introduction. Kidney cancer is the eleventh most common malignancy in the United States of Mexico. Carcinoma renal cell (CRC) is considered the most frequent type and represents 2-3% of all cancers worldwide. In the setting of metastatic disease, a primary renal tumor is usually identified, and metastases are located in the lung, bone, liver, brain, and rarely in soft tissue. Patients with soft tissue metastases do not have symptoms in the initial stages and are generally found only when the lesions increase in size or during the study of the surgical resection piece. Clinical case. In this case, we report a female patient in the seventh decade of life with a soft tissue metastasis located in the sacral region, 10 years after a nephrectomy secondary to CRC. Results. Clinical and radiological findings of a well-defined tumor. Surgical resection of the lesion is performed under regional anesthesia with complete excision. Conclusions. It is recommended that patients with a resectable and solitary metastatic site be candidates for surgical resection with free margins, as was the case with our patient due to its easy access and single lesion. In CRC, in addition to its initial surgical treatment, close surveillance with physical examination and cross-sectional images is essential to monitor the presence of metastases and thus avoid late treatments.

Bilateral choroidal metastasis of follicular thyroid carcinoma 7 years after total thyroidectomy: a case report

ABSTRACT Follicular thyroid cancers account for 15%-20% of all thyroid tumors. Choroidal metastases secondary to follicular thyroid cancer rarely occur. Herein, we report the case of an 85-year-old woman who presented choroidal metastasis from a follicular thyroid carcinoma in the right eye 7 years after total thyroidectomy and underwent enucleation. To confirm the diagnosis and primary tumor site, histopathological, and immunohistochemical examinations were performed. One year later, she presented metastasis in the contralateral eye. Few similar cases have been described in the literature.

Hepatic alveolar echinococcosis simulating metastatic malignancy

ABSTRACT Echinococcosis is a parasitic disease caused by infection with tiny tapeworms of the genus Echinococcus. Echinococcosis is classified as either cystic echinococcosis or alveolar echinococcosis. The common form is a zoonosis from goats and sheep that tends to cause liver lesions. The larval stage of Echinococcus multilocularis causes alveolar echinococcosis/alveolar hydatid disease. It is a zoonosis with field mice and tundra voles as intermediate and wild carnivores like foxes and wolves as definitive hosts. This zoonosis is highly uncommon compared to the other form known as cystic echinococcosis but poses a great human threat if untreated. We report the case of a young man who was working in the Kashmir Valley, North India, and presented with jaundice and right upper quadrant abdominal pain. Computed tomography revealed a large solid-cystic intrahepatic lesion measuring 125x118x123 mm, suggestive of a malignant tumor with central necrosis. A liver biopsy showed necrosis with PAS-positive membranes morphologically consistent with echinococcosis. Alveolar echinococcosis can present as a solid-cystic mass in the liver and can simulate metastatic malignancy.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Differential Diagnosis of Oral Metastases / Diagnóstico Diferencial de las Metástasis Orales

Metastatic lesions in the mouth can resemble common inflammatory lesions. Therefore, we set out to investigate oral metastases whose clinical and imaging characteristics mimicked those of harmless lesions, confusing and delaying the diagnosis. For this, a systematic review was carried out from case reports, case series, and cross-sectional studies in the PubMed/Medline, Scopus, Embase-via Elsevier, Virtual Health Library, Web of Science, and gray literature, using PICO strategy without period restriction. We assessed the quality of studies using the Joanna Briggs Institute assessment tool. A narrative synthesis of the data was carried out. Association analyses using chi-square and Fisher's exact tests were performed, with statistical significance at p<0.05. Most of the lesions came from the lung, breast, kidneys, liver, and thyroid. They affected mainly the mandibles of men, between the fifth and seventh decades of life, causing osteolysis. In soft tissue, there were firm swellings, associated with bleeding. Limitations regarding the heterogeneity of the included studies and the absence of clinic pathological descriptions of the tumors substantially reduced the chance of statistical analysis of the data. Knowing the different possibilities of clinical presentation of oral and maxillofacial metastases is important for the diagnost ic suspicion to occur and diagnostic errors to be avoided. Thus, treatment is instituted and survival can be extended. Protocol registration: PROSPERO CRD42020200696.

Las lesiones metastásicas en la cavidad oral pueden parecer similares a lesiones inflamatorias comunes. Por ello, nos propusimos investigar metástasis orales cuyas características clínicas e imagenológicas simularan las de lesiones inofensivas, confundiendo y retrasando el diagnóstico. Para ello, se realizó una revisión sistemática a partir de reportes de casos, series de casos y estudios transversales en PubMed/Medline, Scopus, Embase-vía Elsevier, Virtual Health Library, Web of Science y literatura gris, utilizando la estrategia PICO sin restricción de periodo. La calidad de los estudios se evaluó mediante la herramienta de evaluación del Instituto Joanna Briggs. Se realizó una síntesis narrativa de los datos. Se realizaron análisis de asociación mediante chi-cuadrado y prueba exacta de Fisher, con significancia estadística en p<0,05. La mayoría de las lesiones procedían de pulmón, mama, riñones, hígado y tiroides. Afectan principalmente a las mandíbulas de los hombres, entre la quinta y la séptima década de la vida, provocando osteólisis. En los tejidos blandos, había hinchazones firmes, asociadas con sangrado. Las limitaciones con respecto a la heterogeneidad de los estudios incluidos y la ausencia de descripciones clinicopatológicas de los tumores redujeron sustancialmente la posibilidad de realizar un análisis estadístico de los datos. Conocer las diferentes posibilidades de presentación clínica de las metástasis orales y maxilofaciales es importante para que se produzca la sospecha diagnóstica y se eviten errores diagnósticos. Por lo tanto, se instituye el tratamiento y se puede prolongar la supervivencia. Registro de protocolo: PROSPERO CRD42020200696.

Adequacy of surgical margins, re-excision, and evaluation of factors associated with recurrence: a retrospective study of 769 basal cell carcinomas

Abstract Background: Achieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC). Objectives: The objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC. Methods: The medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates. Results: Statistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p = 0.004), tumor size (p = 0.023), tumor location in the H zone of the face (p = 0.005), and aggressive histopathological subtype (p = 0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone. Study limitations: Inadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study. Conclusions: Our results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study / Estudo retrospectivo de vida-real, em centro único, para avaliação do comportamento da fosfatase alcalina total após terapia com rádio-223 no câncer de próstata resistente a castração

Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

El factor de transcripción nuclear NF-κB en cáncer

El factor nuclear κB (NF-κB) es una familia de factores de transcripción sumamente importantes que regulan una gran variedad de genes en diferentes procesos de las respuestas inmunitarias e inflamatorias. Esta familia está compuesta por cinco miembros relacionados estructuralmente, y pueden inducir la transcripción de genes diana al unirse a segmentos específicos de ácido desoxirribonucleico (ADN). Las proteínas NF-κB son usualmente secuestradas en el citoplasma por una familia de proteínas inhibidoras, sin embargo, diversas vías de señalización oncogénica pueden activarla y desencadenar fenotipos malignos en las células correspondientes. El objetivo principal de esta revisión es comprender los mecanismos de regulación del factor de transducción NF-κB, su patogénesis y sus posibles blancos terapéuticos en cáncer. Se consultaron diferentes bases de datos que incluyeron PubMed, Scopus y SciELO, desde el año 2000 hasta diciembre del año 2022; se buscaron las referencias bibliográficas en relación con las palabras clave asociadas al factor NF-κB y cáncer, para finalmente desarrollar la revisión. El factor nuclear de transcripción NF-κB es importante en muchas vías de señalización celular, participa en diversos procesos biológicos y sus alteraciones están asociadas a trastornos inmunitarios y cáncer, entre otras patologías. NF-κB se expresa en todos los tipos de células y tejidos, de tal forma que muchas mutaciones oncogénicas contribuyen a la activación de NF-κB en las células tumorales, y son nuevas rutas de investigación terapéuticas para el cáncer. Existen dos vías de señalización diferentes de NF-κB, denominadas vía canónica y la vía alternativa (no canónica), con distintos mecanismos de activación. Los mecanismos oncogénicos en las que participa el factor NF-κB incluyen inflamación crónica, proliferación, apoptosis, angiogénesis, acción sobre células madre del cáncer, metástasis, regulación metabólica y otros mecanismos asociados. En conclusión, existen aún muchas incógnitas sobre los mecanismos y funciones de NF-κB en el contexto celular; el bloqueo completo del factor NF-κB no parece ser una estrategia factible para el tratamiento del cáncer en el momento actual por la diversidad de acciones fisiológicas importantes que se alteran ante su bloqueo. Futuras investigaciones del factor nuclear NF-κB deberían centrarse en la inhibición de la actividad promotora del cáncer, evitando afectar sus funciones fisiológicas normales.

The nuclear factor kappa B (NF-κB) family of transcription factors, which regulates a large range of genes in various immunological and inflammatory response pathways, is of utmost importance. This family consists of five structurally similar members that can activate target genes by attaching to particular regions of deoxyribonucleic acid (DNA). A class of inhibitory proteins usually keep NF-κB proteins in the cytoplasm; however, different oncogenic signaling pathways can activate them and cause malignant phenotypes in the appropriate cells. The main goal of this review article is to understand the regulatory mechanisms of NF-κB transcription factor, its pathogenesis and its potential cancer therapies. From the year 2000 to December 2022, several databases, including PubMed, Scopus and SciELO, were consulted. Finally, the review was developed by searching bibliographic references looking for the keywords related to NF-κB and cancer. The NF-κB transcription factor plays a key role in numerous cell signaling pathways, is involved in a number of biological functions, and its mutations have been linked to cancer and immunological disorders, among other pathologies. Since NF-κB is expressed in all cell types and tissues, many oncogenic mutations can activate NF-κB in tumor cells, opening up new research possibilities for the treatment of cancer. The canonical pathway and the alternative (non-canonical) pathway are two distinct NF-κB signaling pathways with various activation methods. NF-κB is involved in a variety of oncogenic pathways, including chronic inflammation, proliferation, apoptosis, angiogenesis, effect on cancer stem cells, metastasis, metabolic control and other related mechanisms. In conclusion, there are still many unanswered questions regarding the mechanisms and functions of NF-κB in the cellular context. A complete blockade of NF-κB does not appear to be a feasible strategy for the treatment of cancer at this time due to the variety of significant physiological actions that are altered by its blockade. Future research on NF-κB should focus on preventing cancer promotion while preserving the body's natural physiological processes.

Effect of Yin Yang protein 1 transcriptionally regulating acetyl-CoA carboxylase 1 on the cell migration and lipogenesis in ovarian cancer / 肿瘤研究与临床

Objective:To investigate the expression of acetyl-CoA carboxylase 1 (ACC1) in ovarian cancer tissues and cells, and the related mechanisms of the effect of ACC1 on cell migration and lipogenesis in ovarian cancer.Methods:Samples including 1 case of normal ovarian tissue, 1 case of ovarian cancer primary lesion tissue and 1 case of ovarian cancer omentum metastatic tissue diagnosed by pathology examination of patients undergoing surgery resection who admitted to Linyi Cancer Hospital between January 2019 and December 2021 were collected. Immunohistochemistry was used to detect the protein levels of ACC1 and Yin Yang protein 1 (YY1) of all tissues. The PROMO database was used to predict the possible binding sites of YY1 and ACC1 promoter region. Through the assembled viral vector, the HEY cells of human ovarian cancer with ACC1 or YY1 expression [the untreated cells were treated as the negative control (NC)], or knocked down ACC1 or YY1 (the interference sequence sh1, sh2, sh3 was transferred to the target gene, and the negative control sequence shNC was transferred to the interference sequence). Double luciferase reporter gene assay was used to verify the binding sites of YY1 and ACC1 promoter and the activity of transcriptional regulation. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to detect the mRNA and protein expression levels of ACC1 and YY1 in the treated HEY cells, respectively. Transwell assay was used to detect the migration ability of HEY cells. Oil red O staining and Nile red staining were used to detect the lipid droplets in HEY cells.Results:The immunohistochemical scores of ACC1 and YY1 were 0, 2, 8 scores and 0, 4, 6 scores, respectively in normal ovarian tissue, primary lesion of ovarian cancer, and omentum metastatic tissue. Transwell assay showed that the number of invasive HEY cells in ACC1 overexpression group was more than that in NC group [(87.7±7.4) vs. (52.2±4.2), t = 5.19, P = 0.003]. The number of invasive HEY cells in ACC1-sh1 group, and ACC1-sh2 group with the knockdown of ACC1 was less than that in shNC group [(21.2±1.5), (29.7±2.3) vs. (56.2±5.3); t value was 6.41, 3.77; P < 0.001, P < 0.005]. The number of lipid droplets in HEY cells in the ACC1 overexpression group was more than that in the control NC group [Oil red O staining: (301±25) vs. (215±21); Nile red staining: (287±15) vs. (207±10); all P < 0.05]; the number of lipid droplets in HEY cells in ACC1-sh1 and ACC1-sh2 group with the knockdown of ACC1 was less than that in ACC1-shNC group [Oil red O staining: (113±8), (119±12) vs. (195±18); Nile red staining: (82±8), (117±11) vs. (165±17); all P < 0.05]. The result of dual luciferase reporter assay showed that overexpression of YY1 promoted the luciferase activity of the wild type ACC1 promoter region report gene ( P = 0.003), while the luciferase activity of the report gene was inhibited compared with the wild type after the mutation of binding sites of YY1 in ACCI promoter region ( P = 0.008). Western blot results showed that the expression levels of YY1 and ACC1 protein in HEY cells with YY1 overexpression group were higher than those in NC group, which indicated a synergistic increasing trend of both YY1 and ACC1; the expression levels of YY1 and ACC1 protein in YY1-sh1 group, YY1-sh2 group and YY1-sh3 group with the knockdown of YY1 were lower than those in the control YY1-shNC group, which indicated a synergistic decreasing trend of both YY1 and ACC1. Conclusions:ACC1 and YY1 are highly expressed in ovarian cancer metastatic tissues and both show a positive correlation trend. The expression level of ACC1 in vitro has an impact on cell migration and lipogenesis in ovarian cancer via YY1 transcriptionally regulating ACC1.

Progress of ferroptosis in cancer metastasis / 肿瘤研究与临床

Ferroptosis is a newly discovered programmed death mode characterized by the accumulation of lipid peroxide and reactive oxygen species and the increase of free iron, which involves biological processes including glutathione metabolism, iron metabolism, lipid metabolism and oxidative stress. Tumor metastasis is an important feature of tumor malignancy and one of the main causes of recurrence and death in cancer patients. Recent studies have demonstrated that iron death is closely related to tumorigenesis and development and suggested that ferroptosis inducers are expected to be a new strategy for the treatment of cancer metastasis. This paper reviews the regulatory mechanisms related to ferroptosis and its role in the tumor metastasis, invasion, circulation and colonization.

Expressions of serum N-terminal osteocalcin and cytokeratin 5/6 in primary lung cancer patients with bone metastasis and their clinical significances / 肿瘤研究与临床

Objective:To explore the expressions of serum N-terminal osteocalcin (N-MID) and cytokeratin (CK) 5/6 in primary lung cancer patients with bone metastasis and their clinical significances.Methods:The clinical data of 96 patients with primary lung cancer admitted to Chengdu Second People's Hospital between February 2019 to February 2022 were retrospectively analyzed. All patients were divided into the bone metastasis group (38 cases) and the non-bone metastasis group (58 cases) according to whether bone metastasis occurred, and 45 healthy people who underwent physical examination during the same period were treated as the healthy control group. The expression levels of serum N-MID and CK5/6 in the bone metastasis group, the non-bone metastasis group and the healthy control group were compared. Logistic regression was used to analyze the factors affecting bone metastasis in patients with primary lung cancer; receiver operating characteristic (ROC) curve analysis was used to analyze the value of the expression levels of serum N-MID and CK5/6 in predicting bone metastasis in patients with primary lung cancer.Results:The composition ratio of patients with pathological stage Ⅲ-Ⅳ, serum bone-derived alkaline phosphatase and N-MID expression levels in the bone metastasis group were higher than those in the non-bone metastasis group (all P < 0.05). The expression level of serum N-MID in the bone metastasis group and non-bone metastasis group was higher than that in the healthy control group [(26.0±5.3) ng/ml, (15.3±3.1) ng/ml vs. (9.9±1.7) ng/ml, F = 224.27, P < 0.001], and there were statistically significant differences in the serum N-MID expression level of the pairwise comparison among the three groups (all P < 0.05). The expression level of serum CK5/6 in the bone metastasis group and the non-bone metastasis group was lower than that in the healthy control group [(3.6±0.7) ng/ml, (7.3±1.4) ng/ml vs. (10.6±2.4) ng/ml, F = 178.11, P < 0.001], and there were statistically significant differences in the serum CK5/6 expression level of the pairwise comparison among the three groups (all P < 0.05). Multivariate analysis showed that CK5/6, N-MID and bone-derived alkaline phosphatase were independent affecting factors for bone metastasis in patients with primary lung cancer ( OR = 4.088, 3.615, 2.892, all P < 0.05). ROC curve analysis showed that the optimal cut-off values of serum N-MID and CK5/6 expression levels for predicting bone metastasis in patients with primary lung cancer were 18.59 ng/ml and 4.71 ng/ml; the corresponding the area under the curve (AUC) was 0.881 and 0.862, respectively; and the specificity and AUC of the combination of serum N-MID and CK5/6 in predicting the bone metastasis in patients with primary lung cancer was 98.28% and 0.937 (95% CI 0.869-0.977), respectively; the AUC predicted by the combination of both was higher than that by serum N-MID or CK5/6 single (all P < 0.001). Conclusions:The expression levels of serum N-MID and CK5/6 in primary lung cancer patients with bone metastasis are abnormally changed. Clinical detection of serum N-MID and CK5/6 expression levels may be used as sensitive indicators for predicting the bone metastasis in patients with primary lung cancer.

Effect of cone-beam computed tomography image-guidance on the setup errors of stereotactic body radiotherapy for spinal metastatic tumors / 肿瘤研究与临床

Objective:To evaluate the effect of image-guided with cone-beam computed tomography (CBCT) based on volumetric modulated arc therapy (VMAT)-flattening filter free (FFF) on the setup errors of stereotactic body radiotherapy (SBRT) in patients with spinal metastatic tumors.Methods:The clinical data of 15 patients with spinal metastatic tumors who underwent SBRT in Jilin Cancer Hospital from August 2020 to January 2022 were retrospectively analyzed. The radiotherapy dose of bone metastasis was 32 Gy per 4 times and CBCT scanning was performed before and after radiotherapy. Every patient received radiotherapy 4 times; all 15 patients underwent SBRT 60 times in total and 120 CBCT volume images were finally obtained and analyzed. The systematic error (Σ) and random error (σ) were calculated at different correction threshold levels. The translational setup error and rotational setup error at the left-right (X axis), head-foot (Y axis) and front-back (Z axis) directions before and after radiotherapy were compared, which were expressed as Σ ± σ.Results:The pre-SBRT and post-SBRT translational setup errors were (0.14±0.27) cm and (0.07±0.19) cm, respectively ( P<0.001) in the X direction, (-0.05±0.33) cm and (0.00±0.19) cm, respectively ( P = 0.001) in the Y direction, (-0.13±0.19) cm and (-0.02±0.14) cm, respectively ( P = 0.012) in the Z direction. The pre-SBRT and post-SBRT rotational setup errors were (-0.31±0.76)° and (-0.09±0.34)°, respectively ( P < 0.001) in the X direction, (-0.13±0.88)° and (-0.07±0.36) °, respectively ( P < 0.001) in the Y direction, (0.10±0.51)° and (0.16±0.38)°, respectively ( P < 0.001) in the Z direction. Conclusions:CBCT correction could reduce Σ and σof the translational setup and rotational setup, increase the accuracy of SBRT based on VMAT-FFF for patients with spinal metastatic tumors.

Study on the efficacy and influencing factors of pyrotinib in treatment of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer / 肿瘤研究与临床

Objective:To evaluate the efficacy of oral pyrotinib in treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer in the real world, and to explore its influencing factors.Methods:The clinical data of 148 patients with HER2-positive metastatic breast cancer treated with oral pyrrolitinib in Shanxi Cancer Hospital from September 2018 to December 2020 were retrospectively analyzed. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors, version 1.1, and the adverse effects were graded according to the National Cancer Institute common terminology criteria of adverse effects, version 4.0. The Kaplan-Meier method was used to draw progression-free survival (PFS) curves, the patients were stratified by different clinical characteristics, and log-rank test was used for univariate analysis of PFS; the multivariate analysis of PFS was performed using Cox proportional hazards model.Results:The objective response rate (ORR) of 148 patients was 71.6% (106/148), and the disease control rate (DCR) was 89.2% (132/148). The overall median PFS time was 11.0 months (95% CI 10.1-11.9 months), and the median PFS of 19 patients with brain metastases was 10.0 months (95% CI 7.4-12.6 months). The differences in PFS between patients stratified by disease-free interval (DFI), the number of metastatic site and Eastern Cooperative Oncology Group (ECOG) score were statistically significant (all P < 0.05), but the difference in PFS between patients with negative and positive hormone receptor was not statistically significant ( P > 0.05). Multivariate Cox regression analysis showed that DFI (>1 year vs. ≤1 year: HR = 5.254, 95% CI 0.728-37.933, P = 0.046) and ECOG score (≥2 points vs. 0-1 point: HR = 2.454, 95% CI 1.261-4.788, P = 0.008) were independent influencing factors of PFS. The most common ≥grade 3 adverse effects were diarrhea (31 cases, 20.9%) and hand-foot syndrome (38 cases, 25.8%). Conclusions:The pyrotinib has definite efficacy and good safety in the treatment of HER2-positive metastatic breast cancer in the real world, especially for patients with DFI > 1 year and ECOG score 0-1 point, the efficacy and safety are particularly good.

IgG4-related kidney disease complicated with membranous nephropathy in one patient with multiple metastatic lung malignancies / 中华肾脏病杂志

Here we report the diagnosis and treatment of a rare IgG4-related kidney disease with nephrotic syndrome as the first manifestation. A 62-year-old male patient, presented with edema in both lower limbs and foam urine, had a history of "lung malignant tumor with brain and lymph node metastasis". The increase of IgG4 and decrease of glomerular filtration rate were detected at admission, and the pathological consideration of renal biopsy was membranous nephropathy with IgG4-related tubulointerstitial nephritis. After the combination of low-dose glucocorticoids therapy and rituximab treatment, the patient showed good prognosis in a 9 month follow-up.

Diagnosis of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology / 中华神经科杂志

Endometrial carcinoma is one of common malignant tumors in female reproductive system, but it is extremely rare in leptomeningeal metastasis. The clinical manifestations and signs of meningeal carcinomatosis are complex and not specific. It is difficult to get a precise diagnosis early, and it has high rate of misdiagnosis and missed diagnosis. Accurate diagnosis and treatment of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology are reported. The patient is an elderly female with a history of endometrial cancer. The main manifestations were fever, headache and dizziness; cerebrospinal fluid cytology showed tumor cells; AKT1 gene and TP53 gene were detected in endometrial carcinoma tissue, plasma and cerebrospinal fluid by next-generation sequencing. After treatment with intrathecal chemotherapy, immunotherapy combined with anti angiogenesis, the patient′s condition still progressed gradually and died finally. The purpose of this case report is to raise clinical awareness of recognition and treatment in early meningeal metastasis of endometrial carcinoma.

Effect of intraoperative cell salvage on the number and viability of cancer cells in salvaged autologous blood from patients undergoing liver cancer surgery / 中华麻醉学杂志

Objective:To evaluate the effect of intraoperative cell salvage (ICS) on the number and viability of cancer cells in salvaged autologous blood from the patients undergoing liver cancer surgery.Methods:Twenty patients undergoing open radical primary hepatocellular carcinoma were selected, and blood from the operative field was collected after exposing the liver and treated with ICS. Blood specimens 20 ml from the surgical field (S 1), blood specimens 20 ml before ICS treatment-leukocyte depletion filter (LDF) filtration (S 2) and blood specimens 20 ml after LDF filtration (S 3) were collected and enriched, of which the blood sample 10 ml was used for cancer cell identification and count by immunofluorescence staining, and the remaining blood sample 10 ml was continuously cultured for 3 weeks, and then cell viability was observed by immunofluorescence method. Results:Hepatocellular carcinoma(HCC) cells were identified in 19 S 1 specimens, 18 S 2 specimens, and 16 S 3 specimens, but there was no significant difference in the detection rate among the three specimens ( P>0.05). Compared with S 1 specimens, HCC cell count was significantly reduced in S 2 and S 3 specimens ( P<0.05). There was no significant difference in the HCC cell count between S 3 specimens and S 2 specimens ( P>0.05). After 3 weeks of culture, the results of light microscopy showed that: hepatocellular carcinoma cell clusters were found in S1 specimens, and no hepatocellular carcinoma cell cluster was found in S 2 and S 3 specimens; the results of fluorescence microscopy showed that: 400 and 14 mixed epithelial-mesenchymal HCC cells and 100 and 21 mesenchymal HCC cells were found in S 1 and S 2 specimens, respectively, while no HCC cells were identified in S 3 specimens, among which HCC cells mainly presented as clusters of hepatocellular carcinoma cells in S 1 specimen, while no clusters of hepatocellular carcinoma cells were found in S 2 and S 3 specimens. Conclusions:After treatment with ICS or ICS-LDF, the number and viability of hepatocellular carcinoma cells in salvaged autologous blood are significantly reduced, and hepatocellular carcinoma cells exist as single cells and fail to develop clusters of hepatocellular carcinoma cells; LDF can reduce the risk of hepatocellular carcinoma cell autotransfusion to a certain extent, although it can not effectively filter out hepatocellular carcinoma cells continuously.

Development of a nomogram for predicting lymph node metastasis of colorectal tumors in preoperative period / 中华老年医学杂志

Objective:The purpose of this study is to construct and validate a simple and accurate clinical nomogram for predicting preoperative lymph node metastasis(LNM)in individualized patients with colorectal cancer.Methods:The clinical data of patients came from SEER database, and Logistic regression model was used to build a prediction model.The accuracy of nomograph was evaluated and tested by receiver operating characteristic curve(ROC)curve and calibration curve.Results:78584 eligible colorectal cancer(CRC)patients in SEER database were enrolled in this study.The risk factors related to lymph node metastasis include diagnostic age, T stage, M stage, tumor grade and carcinoembryonic antigen(CEA)level.The model showed good accuracy, with an AUC value of 0.734(95% CI, 0.730-0.741). In the validation queue, the model can still reach a high AUC value of 0.728(95% CI, 0.722-0.734). Conclusions:Age, T stage, M stage, tumor grade and CEA level are independent risk factors for lymph node metastasis of colorectal cancer.The nomogram established based on these factors can predict the probability of lymph node metastasis of colorectal cancer.

Predictive value of pre-surgical 18F-FDG PET/CT metabolic parameters for mediastinal lymph node metastasis in patients with lung adenocarcinoma / 中华核医学与分子影像杂志

Objective:To investigate predictive value of model based on pre-surgical 18F-FDG PET/CT metabolic parameters for mediastinal lymph node metastasis (LNM) in lung adenocarcinoma. Methods:A total of 288 patients with lung adenocarcinoma (135 males, 153 females, age (61.6±8.5) years) who diagnosed and treated in the Fourth Hospital of Hebei Medical University from January 2016 to February 2021 were enrolled retrospectively. All patients underwent 18F-FDG PET/CT examination within 1 month before operation, and underwent complete resection of primary lung tumor and standard lymph node dissection. PET/CT parameters were extracted (PET metabolic parameters: minimum SUV(SUV min), SUV max, SUV mean, SUV standard deviation (SUV std), metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT parameters: minimum CT value (HU min), maximum CT value (HU max), mean CT value (HU mean), CT value standard deviation (HU std)). Multivariate logistic regression analysis was used for screening parameters and establishing model to predict LNM. ROC curves analyses were used to evaluate the predictive performance of models. Results:Among 288 patients, 90 had LNM, and 361 metastatic lymph nodes (N1: 186, N2: 175) were reported by pathology. SUV min (odds ratio ( OR)=1.859, 95% CI: 1.074-3.220, P=0.027), SUV max ( OR=2.255, 95% CI: 1.306-3.893, P=0.004), SUV mean ( OR=0.277, 95% CI: 0.115-0.665, P=0.004) were predictors of LNM. The AUC of PET/CT model was 0.849 (95% CI: 0.804-0.893), and the sensitivity, specificity, accuracy, and positive and negative predictive values were 87.8%(79/90), 72.2%(143/198), 77.1%(222/288), 59.0%(79/134) and 92.9%(143/154), respectively. Conclusion:The model based on 18F-FDG PET/CT metabolic parameters can improve the accuracy of pre-surgical N-staging in patients with lung adenocarcinoma.

Efficacy and safety analysis of anlotinib in the treatment of distant metastatic radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the efficacy and safety of anlotinib in distant metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:Retrospective analysis was performed on 17 patients with distant metastatic RAIR-DTC (6 males, 11 females, age: 57.0(45.5, 63.0) years) from Affiliated Hospital of Qingdao University between October 2018 and February 2023, including 13 patients receiving first-line treatment and 4 patients receiving second-line treatment with anlotinib. The changes of serum thyroglobulin (Tg) during the treatment of anlotinib, the changes of maximum diameter of the target lesion at the last follow-up compared with the diameter at baseline, the imaging efficacy, and treatment-related adverse events were analyzed. The serological and imaging effects of the first-line treatment group and the second-line treatment group were compared. The Fisher exact test was used to analyze the differences between groups.Results:The follow-up time of 17 patients was 17.3(9.5, 21.4) months, and the objective response rate (ORR) and disease control rate (DCR) were 7/17 and 16/17, respectively. There were no significant differences of ORR (6/13 vs 1/4; P=0.603) and DCR (13/13 vs 3/4; P=0.235) between the first-line and second-line treatment groups. The change rates of serum Tg at 3, 6 weeks and the last follow-up were -30.2%(-61.2%, -15.5%), -64.8%(-90.6%, -32.3%), and -85.8%(-96.1%, -50.7%), respectively. At the last follow-up, the change rate of maximum diameter of target lesions was -20.0%(-45.0%, -5.2%). The incidence of treatment-related adverse reactions was 14/17, and 2 patients (2/17) had grade 3 or above adverse reactions. Conclusion:Anlotinib shows superior efficacy with tolerable toxicity in the first-line treatment of distant metastatic RAIR-DTC, and hopefully plays an important role in second-line treatment for RAIR-DTC resistant to sorafenib.

Study of 68Ga-NODAGA-RGD PET/CT in predicting short-term efficacy of tyrosine kinase inhibitor in the treatment of distant metastatic differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the clinical application of 68Ga-cyclo( L-arginylglycyl- L-α-aspartyl- D-tyrosyl-N6-(((4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)acetyl))- L-lysyl) (NODAGA-RGD) PET/CT to evaluate short-term efficacy of tyrosine kinase inhibitor (TKI) in distant metastatic differentiated thyroid cancer (dmDTC). Methods:From October 2019 to March 2023, 13 dmDTC patients (5 males, 8 females; age: 68(65, 69) years) from Nanjing First Hospital were retrospectively enrolled, of which 9 were clinically confirmed as radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and 4 were dmDTC without radioactive iodine treatment. All patients underwent 68Ga-NODAGA-RGD PET/CT to assess neovascularization of the target lesions (TL), and the SUV max and target background ratio (T/B) were recorded. After 3 months of TKI treatment (anrotinib ( n=9) or apatinib ( n=4)), change rates of the maximum diameter of TL and thyroglobulin (Tg) were measured. The correlation of SUV max, T/B and the change rate of the maximum diameter of TL were analyzed by Spearman rank correlation analysis. ROC curve analysis was performed for the effectiveness of the T/B and TKI therapy, and the difference of the remission rate of lesions was analyzed by Fisher exact test. Results:In 13 patients, 36 TL were measured by 68Ga-NODAGA-RGD PET/CT with SUV max of 5.44(3.43, 7.56) and T/B of 5.25(4.50, 7.23). The change rate of the maximum diameter of TL was -30%(-39%, -21%) and the change rate of Tg was -68%(-96%, -52%). T/B was negatively correlated with the change rate of the maximum diameter of TL after TKI therapy ( rs=-0.46, P=0.005), while SUV max was not correlated with the change rate of the maximum diameter of TL ( rs=0.03, P=0.883). ROC curve analysis showed that the optimal cut-off value for T/B was 4.95, with the AUC of 0.698, the sensitivity of 87.5%, and the specificity of 60.0%. Compared to lesions with T/B<4.95, those with T/B≥4.95 showed higher remission rate (2/14 vs 63.6%(14/22); P=0.006). After 3 months of TKI treatment, the disease control rate was 12/13. Conclusion:68Ga-NODAGA-RGD PET/CT can effectively reflect tumor neovascularization, predict efficacy of TKI therapy, and provide powerful imaging evidence for TKI therapy in dmDTC.